Abstract
Multidomain proteins with flexible linkers and disordered regions play important roles in many cellular processes, but characterizing their conformational ensembles is difficult. We have previously shown that the coarse-grained model, Martini 3, produces too compact ensembles in solution, that may in part be remedied by strengthening protein–water interactions. Here, we show that decreasing the strength of protein–protein interactions leads to improved agreement with experimental data on a wide set of systems. We show that the ‘symmetry’ between rescaling protein–water and protein–protein interactions breaks down when studying interactions with or within membranes; rescaling protein-protein interactions better preserves the binding specificity of proteins with lipid membranes, whereas rescaling protein-water interactions preserves oligomerization of transmembrane helices. We conclude that decreasing the strength of protein–protein interactions improves the accuracy of Martini 3 for IDPs and multidomain proteins, both in solution and in the presence of a lipid membrane.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 6645 |
| Tidsskrift | Nature Communications |
| Vol/bind | 15 |
| Udgave nummer | 1 |
| Antal sider | 17 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:We acknowledge the use of computational resources from Computerome 2.0, the ROBUST Resource for Biomolecular Simulations (supported by the Novo Nordisk Foundation grant no. NF18OC0032608), and the core facility for biocomputing at the Department of Biology. This research was supported by the Lundbeck Foundation BRAINSTRUC initiative (R155-2015-2666 to K.L.-L.) and the PRISM (Protein Interactions and Stability in Medicine and Genomics) centre funded by the Novo Nordisk Foundation (NNF18OC0033950, to K.L.-L.). SV and AK acknowledge support by the Swiss National Science Foundation through the National Center of Competence in Research Bio-Inspired Materials. This work was supported by grants from the Swiss National Supercomputing Centre (CSCS) under project ID s1176 and s1251.\u00A0This project has received funding from the European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation programme (Grant agreement No. 803952 to SV).
Publisher Copyright:
© The Author(s) 2024.